Regional changes in ventilation and perfusion occurring in the early hours after smoke inhalation injury were evaluated through the use of positron emission tomography. Five lambs were imaged before and 1, 2, and 4 h after receiving 100 breaths of cotton smoke. Utilizing a recently developed model of (13)N tracer kinetics (3), we evaluated changes in ventilation, perfusion, shunt, and regional gas content in nondependent, middle, and dependent lung zones. The data demonstrated a progressive development of regional shunt in dependent (dorsal) regions in which perfusion remained the highest throughout the study. These findings, together with decreasing regional ventilation and fractional gas content in the dependent regions, correlated with decreasing arterial Pa(O(2)) values over the course of the study. A negative correlation between regional shunt fraction and regional gas content in dependent and middle regions suggests that shunt was caused by progressive alveolar derecruitment or flooding.